Results of a new international phase 4 study of patients with nosocomial pneumonia due to proven methicillin-resistant Staphylococcus aureus (MRSA) demonstrated that the antibiotic Zyvox® (linezolid) achieved a statistically significantly higher clinical success rate compared with vancomycin for the primary endpoint. The ZEPHyR (Linezolid in the treatment of subjects with nosocomial pneumonia proven to be due to methicillin-resistant Staphylococcus aureus) study was the largest ever conducted in this population. These findings were presented at the 48th annual meeting of the Infectious Diseases Society of America (IDSA) in Vancouver last week.
Investigators from 156 centers worldwide randomized 1,225 patients, of whom 448 patients had proven MRSA nosocomial pneumonia (modified intent-to-treat group); 339 patients also met key protocol criteria at the end of study (per-protocol group) and were included in the primary analysis. Clinical success rates at the end of study were 57.6 percent (95/165) for patients treated with Zyvox compared with 46.6 percent (81/174) for patients treated with vancomycin in the per-protocol group, the primary endpoint. These results demonstrated that Zyvox achieved a statistically significantly higher clinical success rate compared to vancomycin (95 percent confidence interval for the difference in response rates: 0.5 percent, 21.6 percent; p=0.042). Results were consistent for the per-protocol group at end of treatment and for all MRSA pneumonia subjects (modified intent-to-treat) at end of treatment and end of study. Microbiologic success was also consistent in both the per-protocol and the modified intent-to-treat groups at both end of treatment and end of study.
Nosocomial pneumonia continues to be a significant cause of illness, and when these infections are due to MRSA, our options are limited, as there are few antibiotics that are effective against this resistant organism, says study investigator Dr. Jean Chastre, professor of medicine and critical care medicine at University Paris 6, Réanimation Médicale, Pitié-Salpêtrière Hospital in Paris. The findings, which show a higher cure rate for linezolid compared with vancomycin, provide important information for physicians who treat nosocomial pneumonia caused by MRSA.
Treatment-related adverse events reported in 1 percent or more of Zyvox patients were diarrhea (3.7 percent), rash (2.7 percent), constipation (1.0 percent) and nausea (1.0 percent). Treatment-related adverse events reported in 1 percent or more of vancomycin patients were diarrhea (4.3 percent), nausea (1.9 percent), rash (1.7 percent), anemia (1.4 percent) and acute renal failure (1.4 percent). Overall, 208 patients in each group reported serious adverse events; these were considered treatment-related in five Zyvox patients and 13 vancomycin patients. Deaths occurred in 18.3 percent of patients who received Zyvox and 19.4 percent of patients who received vancomycin. Adverse events were considered treatment-related for 16.2 percent of Zyvox patients and 18.4 percent of vancomycin subjects. Treatment-related adverse events, serious adverse events and deaths were comparable for Zyvox and vancomycin. Safety data were assessed in all patients who received at least one dose of study drug, the intent-to-treat group (N=1,184). An estimated 1.7 million healthcare-associated infections are reported in U.S. hospitals annually, and about 16 percent of those are associated with pathogens that are resistant to the antimicrobials traditionally used to treat them, including MRSA. In a review of invasive MRSA cases reported in nine U.S. communities participating in the Centers for Disease Control and Preventions Active Bacterial Core surveillance program, healthcare-associated pneumonia accounted for between 12 percent and 16 percent of all healthcare-associated invasive MRSA infections.
Pfizer is committed to research in infectious diseases, and data from this large comparative study add to the body of evidence for Zyvox in the treatment of MRSA nosocomial pneumonia and reinforce its efficacy in this patient population, says Dr. Mark Kunkel, executive director of the Clinical Group Lead for Anti-infective Drugs, Specialty Care Business Unit, Pfizer.